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The circadian clock in mammals
No full textThe basic physiological and anatomical basis for circadian rhythms in mammalian
behaviour and physiology is introduced. The pathways involved in photic
entrainment of the circadian clock are discussed in relation of new findings that
identify the molecules that are involved in signalling between the environment
and the clock. The molecular basis of endogenous cycles is described in the
mouse, and compared to the mechanism that is present in the fly. Finally we
speculate on the relationship between circadian physiology and pain
Comparative analysis of circadian clock genes in insects
Full text linkAfter a slow start, the comparative analysis of clock genes in insects has developed into a mature area of study in recent years. Brain transplant or surgical interventions in larger insects defined much of the early work in this area, before the cloning of clock genes became possible. We discuss the evolution of clock genes, their key sequence differences, and their likely modes of regulation in several different insect orders. We also present their expression patterns in the brain, focusing particularly on Diptera, Lepidoptera, and Orthoptera, the most common non-genetic model insects studied. We also highlight the adaptive involvement of clock molecules in other complex phenotypes which require biological timing, such as social behaviour, diapause and migration
Evolution of behavioral genes
No full textBehavioral genetics has come a long way since it started to be taken semi-seriously in the 1950s. In the early days, selection experiments and studies of highly inbred strains tended to provide the major experimental approaches. These had a distinctly evolutionary flavor in that crosses between selected or inbred lines would be used to determine the “genetic architecture” of a phenotype, and to provide some indirect evidence for the selective forces underlying the trait in question, be it sexual behavior in flies or aggression in mice (Hay 1985). In the 1970s, Seymour Benzer advocated the “neurogenetic” approach with its emphasis on single genes, and which used behavior as an entrée into the dissection of the nervous system of the fruit fly, Drosophila melanogaster (Benzer 1971). With the coming of the molecular era in the 1980s, the cloning and sequencing of these “behavioral” genes, allied to the transgenic technology mediated by P-elements, added a further spectacular dimension to fly neurogenetics. This has been further exploited by the use of the Gal4/UAS misexpression systems that can be targeted to specific neurons (Brand and Perrimon 1993). Thus, the “brain to behavior” pathway in the fly can now be analyzed at almost all biological levels, from DNA through biochemistry, cellular biology, anatomy, and physiology. However, similar technical developments in mice and worms mean that these types of sophisticated manipulations can be extended to vertebrates and nematodes
Molecular analysis of circadian clocks in Drosophila simulans
No full textThe Drosophila simulans per gene is polymorphic for the length of a repeat that encodes a series of Thr-Gly pairs. We have examined the circadian behaviour of flies derived from isofemale lines that carry the major variants, and find some significant differences in the way that the clock responds to temperature challenge, that might relate to the observed frequencies of these alleles in nature. We also observe that circadian thermal behaviour is also predictably influenced by subtle differences in the temperature of the locality from which these flies have been originally collected. There appear to be species-specific differences in the circadian locomotor patterns of D. melanogaster and D. simulans and in the way they may respond to temperature. Using chimeric per transgenes which carry the different species Thr-Gly fragments, we have been able to identify components of the behaviour that are modulated by this region of the PER protein
A latitudinal cline in a Drosophila clock genein a Drosophila clock gene
No full textThe clock gene period determines biological rhythmicity in Drosophila melanogaster and encodes a protein characterized by an alternating series of threonine-glycine pairs. The minisatellite region encoding the threonine-glycine repeat is polymorphic in length in natural Drosophila melanogaster populations. In this paper we report the geographical analysis of this polymorphism within Europe and North Africa. A robust clinal pattern is observed along a north-south axis. We suggest the possibility that the length polymorphism could be maintained by thermal selection because the threonine-glycine region has been shown to provide thermostability to the circadian phenotyp
A constitutively active cryptochrome in Drosophila melanogaster
No full textLight-activated cryptochrome (CRY) regulates circadian photoresponses in Drosophila melanogaster. Removing the carboxy (C) terminus to create CRYDelta produces, in yeast, a light-independent, constitutively active form. Here we show that flies overexpressing CRYDelta have a longer free-running period of locomotor activity, as well as altered cycling kinetics of the clock proteins timeless (TIM) and period (PER). Moreover, at the cellular level, they show a reduction in the level of TIM and in the nuclear localization of TIM and PER in two significant clusters of behavioral pacemaker cells: the large and the small ventral lateral neurons (LN(v)s). These effects are similar to those seen in wild-type flies under continuous light and suggest a regulatory role for the C terminus of CRY on the photosensitive, photolyase-like part of the protein
Molecular polymorphism in the period gene of Drosophila simulans.
No full textThe threonine-glycine (Thr-Gly) repeat region of the period (per) gene of eight natural populations of Drosophila simulans from Europe and North Africa was analyzed by polymerase chain reaction, DNA sequencing and heteroduplex formation. Five different length alleles encoding 21, 23, 25 and two different kinds of 24 Thr-Gly pairs in the uninterrupted repeat were found. In the 3' region flanking the repeat 6 nucleotide substitutions (3 synonymous, 3 replacement) were observed in three different combinations that we called haplotypes I, II and III. The complete linkage disequilibrium observed between the haplotypes and these length variants allowed us to infer from the repeat length, the DNA sequence at the 3' polymorphic sites. The haplotypes were homogeneously distributed across Europe and North Africa. The data show statistically significant departures from neutral expectations according to the Tajima test. The results suggest that balancing selection might have played a role in determining the observed levels and patterns of genetic diversity at the per gene in D. simulans
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